Molecular and epigenetic pathogenesis of germ cell tumors DOI Creative Commons
Melanie Müller, Margaretha A. Skowron, Peter Albers

et al.

Asian journal of urology, Journal Year: 2020, Volume and Issue: 8(2), P. 144 - 154

Published: May 30, 2020

The development of germ cell tumors (GCTs) is a unique pathogenesis occurring at an early developmental stage during specification, migration or colonization primordial cells (PGCs) in the genital ridge. Since driver mutations could not be identified so far, involvement epigenetic machinery seems to play crucial role. Currently, it investigated whether modifications between omnipotent two-cell and pluripotent implanting PGCs might result disturbances eventually leading GCTs. Although progress understanding mechanisms PGC ongoing, little known about complete picture its GCT eventual classification into clinical subtypes. This review will shed light current knowledge complex molecular contribution GCTs by emphasizing on stages until arrival late gonads. We questioned how misguided migrating and/or colonizing develop either type I II Additionally, we asked pluripotency can regulated which changes contribute pathogenesis. propose that SOX2 SOX17 determine embryonic stem cell-like (embryonal carcinoma) PGC-like fate (seminoma). Finally, suggest factors secreted microenvironment, i.e. BMPs BMP inhibiting molecules, dictate decision neoplasia situ (into seminoma embryonal seminomas carcinoma extraembryonic lineage), indicating important role microenvironment plasticity.

Language: Английский

A Summary of the Inaugural WHO Classification of Pediatric Tumors: Transitioning from the Optical into the Molecular Era DOI Creative Commons
Stefan M. Pfister, Miguel Reyes‐Múgica, John K. C. Chan

et al.

Cancer Discovery, Journal Year: 2021, Volume and Issue: 12(2), P. 331 - 355

Published: Dec. 17, 2021

Abstract Pediatric tumors are uncommon, yet the leading cause of cancer-related death in childhood. Tumor types, molecular characteristics, and pathogenesis unique, often originating from a single genetic driver event. The specific diagnostic challenges childhood led to development first World Health Organization (WHO) Classification Tumors. classification is rooted multilayered approach, incorporating morphology, IHC, characteristics. volume organized according organ sites provides single, state-of-the-art compendium pediatric tumor types. A special emphasis was placed on “blastomas,” which variably recapitulate morphologic maturation organs they originate. Significance: In this review, we briefly summarize main features updates each chapter inaugural WHO Tumors, including its rapid transition mostly microscopic into molecularly driven systematically taking recent discoveries genomics account.

Language: Английский

Citations

137
Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy DOI Creative Commons
Matin Chehelgerdi,

Fereshteh Behdarvand Dehkordi,

Mohammad Chehelgerdi

et al.

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Nov. 28, 2023

The advent of iPSCs has brought about a significant transformation in stem cell research, opening up promising avenues for advancing cancer treatment. formation is multifaceted process influenced by genetic, epigenetic, and environmental factors. offer distinctive platform investigating the origin cancer, paving way novel approaches to treatment, drug testing, tailored medical interventions. This review article will provide an overview science behind iPSCs, current limitations challenges iPSC-based therapy, ethical social implications, comparative analysis with other types also discuss applications tumorigenesis, future tumorigenesis highlight successful case studies utilizing research. conclusion summarize advancements made research importance continued investment iPSC unlock full potential these cells.

Language: Английский

Citations

68
EANO, SNO and Euracan consensus review on the current management and future development of intracranial germ cell tumors in adolescents and young adults DOI Creative Commons
Didier Frappaz, Girish Dhall, Matthew J. Murray

et al.

Neuro-Oncology, Journal Year: 2021, Volume and Issue: 24(4), P. 516 - 527

Published: Oct. 28, 2021

The incidence of intracranial germ cell tumors (iGCT) is much lower in European and North American (E&NA) than Asian population. However, E&NA cooperative groups have simultaneously developed with success treatment strategies specific attention paid to long-term sequelae. Neurological sequelae may be reduced by establishing a diagnosis an endoscopic biopsy and/or cerebrospinal fluid (CSF) serum analysis, deferring the need perform radical surgery. Depending on markers histological characteristics, patients are treated as either germinoma or non-germinomatous (NGGCT). Metastatic disease defined positive CSF cytology distant drops craniospinal MRI. combination surgery chemotherapy radiation therapy tailored according grouping staging. With more 90% 5-year event-free survival (EFS), localized germinomas can managed without aggressive surgery, benefit from followed whole ventricular irradiation local boost. Bifocal non-metastatic entities. cured irradiation. EFS over 70%, NGGCT delayed case residual disease, some form radiotherapy. Future will aim at decreasing side effects while preserving high cure rates.

Language: Английский

Citations

100
Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data DOI Creative Commons
João Lobo,

Ad Gillis,

Annette van den Berg

et al.

Cells, Journal Year: 2019, Volume and Issue: 8(12), P. 1637 - 1637

Published: Dec. 14, 2019

Liquid biopsy-based biomarkers, such as microRNAs, represent valuable tools for patient management, but often do not make it to integration in the clinic. We aim explore issues impeding this transition, setting of germ cell tumors, which novel biomarkers are needed. describe a model identifying and validating clinically relevant microRNAs tumor patients, using both vitro, vivo (mouse model) patient-derived data. Initial wide screening candidate is performed, followed by targeted profiling potentially biomarkers. demonstrate relevance appropriate (negative) controls, experimental conditions (proliferation), related sample origin (serum, plasma, cerebral spinal fluid) pre-analytical variables (hemolysis, contaminants, temperature), all could interfere with liquid studies their conclusions. Finally, we show value our identification specific scenario, contradicting presumed role miR-375 marker teratoma histology biopsy setting. Our findings indicate other putative (miR-885-5p, miR-448 miR-197-3p) fulfilling clinical need. The informative identify best pursue

Language: Английский

Citations

92
Application of miRNAs in the diagnosis and monitoring of testicular germ cell tumours DOI
Kristian Almstrup, João Lobo, Nina Mørup

et al.

Nature Reviews Urology, Journal Year: 2020, Volume and Issue: 17(4), P. 201 - 213

Published: March 10, 2020

Language: Английский

Citations

83
The consequences of recurrent genetic and epigenetic variants in human pluripotent stem cells DOI Creative Commons
Peter W. Andrews, Ivana Barbaric, Nissim Benvenisty

et al.

Cell stem cell, Journal Year: 2022, Volume and Issue: 29(12), P. 1624 - 1636

Published: Dec. 1, 2022

Language: Английский

Citations

54
DMRT1 regulates human germline commitment DOI Creative Commons
Naoko Irie, Sun-Min Lee, Valentina Lorenzi

et al.

Nature Cell Biology, Journal Year: 2023, Volume and Issue: 25(10), P. 1439 - 1452

Published: Sept. 14, 2023

Abstract Germline commitment following primordial germ cell (PGC) specification during early human development establishes an epigenetic programme and competence for gametogenesis. Here we follow the progression of nascent PGC-like cells derived from embryonic stem in vitro. We show that switching BMP signalling PGC to Activin A retinoic acid resulted DMRT1 CDH5 expression, indicators migratory PGCs vivo. Moreover, induction SOX17 promoted resetting with striking global enrichment 5-hydroxymethylcytosine locus-specific loss 5-methylcytosine at binding sites expression DAZL representing DNA methylation-sensitive genes, a hallmark germline programme. provide insight into unique role advances biology vitro

Language: Английский

Citations

23
Exploring the microbiome-gut-testis axis in testicular germ cell tumors DOI Creative Commons
Sona Ciernikova, Aneta Sevcikova, Michal Mego

et al.

Frontiers in Cellular and Infection Microbiology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 9, 2025

The microbiome-gut-testis axis has emerged as a significant area of interest in understanding testicular cancer, particularly germ cell tumors (TGCTs), which represent the most common malignancy young men. interplay between gut and microbiomes is hypothesized to influence tumorigenesis reproductive health, underscoring complex role microbial ecosystems disease pathology. encompasses interactions microbiome, systemic immune modulation, local microenvironment testis. Dysbiosis or may contribute altered responses, inflammation, hormonal imbalances, potentially playing pathogenesis TGCTs. Concurrently, seminal have been linked variations sperm quality, fertility potential, possibly cancer susceptibility, need for further evaluation. This review explores emerging context highlighting its implications onset, progression, treatment efficacy, toxicity. Identifying potential biomarkers, followed by microbiota modulation restore balanced community, might offer novel supportive strategy improving efficacy refractory TGCT patients while reducing chemotherapy-induced We suggest better association dysregulated environments TGCTs emphasizes pathways microbiome cancer.

Language: Английский

Citations

1
Organoid drug profiling identifies methotrexate as a therapy for SCCOHT, a rare pediatric cancer DOI Creative Commons
Seok-Young Kim, Tamar A. E. de Weert, Marijn A. Vermeulen

et al.

Science Advances, Journal Year: 2025, Volume and Issue: 11(9)

Published: Feb. 26, 2025

Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare and lethal tumor in adolescent young adult patients. Now, there no standard-of-care treatment for these Reliable models that represent this disease can be used translational research are scarce. To model SCCOHTs, we have established eight patient-derived tumoroid lines from lesions three patients with SCCOHT. The tumoroids recapitulate genomic transcriptomic characteristics corresponding patient tumors capture intrapatient heterogeneity. Organoid drug profiling using library 153 clinical compounds identified methotrexate as an effective selective against SCCOHTs clinically relevant IC 50 35 nanomolars. RNA sequencing demonstrated induced TP53 pathway activation apoptosis. These data underscore organoid technology support design therapeutic strategies cancers.

Language: Английский

Citations

1
Long‐term expansion with germline potential of human primordial germ cell‐like cells in vitro DOI Open Access
Yusuke Murase, Yukihiro Yabuta, Hiroshi Ohta

et al.

The EMBO Journal, Journal Year: 2020, Volume and Issue: 39(21)

Published: Sept. 20, 2020

Language: Английский

Citations

51